Radiotherapy For Early Breast Cancer Research Articles

Estimated Absolute Risks from Typical UK Radiotherapy for Early Breast Cancer During 2015–2023

Estimated Absolute Risks from Typical UK Radiotherapy for Early Breast Cancer During 2015–2023

Comparison of the effectiveness of intraoperative radiotherapy with external beam radiotherapy in patients with early breast cancer

Background. Breast cancer is the most common cancer in women. The main treatment for breast cancer includes surgery, chemotherapy, radiation therapy, and hormone therapy. The role of radiation therapy in the management of breast cancer continues to evolve. Radiation therapy is currently being de-escalated to include the use of intraoperative radiotherapy (IORT) and adjuvant endocrine therapy. Purpose of the study: to compare the efficacy of IORT with that of external beam radiotherapy (EBRT) in the treatment of early breast cancer. Material and Methods. A retrospective study of 559 patients with early breast cancer was conducted in Clinical Oncology Center of Saint Petersburg. The main treatment group included 273 patients who underwent breast-conserving surgery with IORT and sentinel lymph node biopsy. The control group included 286 patients who underwent breast-conserving surgery with sentinel lymph node biopsy and EBRT. Results. For all patients, the median follow-up time was 59.1 months (interquartile range: 43.7 to 80.7), the minimum follow-up period was 0.6 months, and the maximum follow-up period was 110.4 months. Recurrence occurred in 18 (6.6 %) patients of the main group and in 8 (2.8 %) patients of the control group. A statistically significant association of biological subtype with survival outcomes was found (p=0.02). The hazard ratio for Luminal B of 1.88 (95 % CI 1.02, 3.46) corresponded to a 65 % chance of an earlier onset of a negative outcome. The hazard ratio for triple-negative breast cancer of 3.01 (95 % CI 1.53, 5.95) corresponded to a 75 % chance of an earlier negative outcome. In the main treatment group, 11 (4 %) patients developed disease progression, and 2 of them died of multiple organ failure. In the control group, disease progression was observed in 18 (6.3 %) patients, 6 of whom died. However, the analysis of overall survival using the Kaplan–Meier curve showed a statistically non-significant log-rank p-value (0.73). The 3-year survival rates were 100 % (100 – 100) in the treatment group and 98.2 % (96.7 – 99.8) in the control group. The 5-yaer survival rates were 99.3 % (97.9 – 100) in the treatment group and 97.8 % (96.2 – 99.6) in the control group. These results showed advantage of IORT over EBRT. Conclusions. Intraoperative radiotherapy is a safe and effective alternative to external beam radiotherapy for early breast cancer.

Quality of Life Outcomes Associated With Optimization of Treatment by Omitting Radiotherapy in Early Breast Cancer

PurposeImproved prognosis of early breast cancer (EBC) has created opportunities for treatment optimization but reducing morbidity should not inadvertently compromise quality of life (QoL). PROSPECT1 used pre-operative MRI and pathology findings to identify women suitable for radiotherapy (RT) omission following breast conserving surgery. We retrospectively explored the association between de-escalation by omission of RT and QoL in women with EBC. Materials and methodsThree groups were recruited: PROSPECT participants who omitted RT following preoperative MRI (A); participants who received RT following preoperative MRI (B); and women who received usual care - No MRI, received RT (C). Measures included the EORTC QLQ-C30 and BR23, BCTOS, DASS-21 and a measure of decision regret. Between group differences were assessed using ANOVA or nonparametric equivalents. Semi-structured interviews were analyzed with qualitative description (n = 44). ResultsData from 400 women were analyzed (125A, 102B, 173C). Group A had fewer symptoms and better body image (breast symptoms: A-B P = .003, A-C P = <.001; arm symptoms: A-B P = .004, A-C P = .011; body image: A-C P = .041) and fewer differences between the treated and untreated breasts (cosmetic: A-B P < .001, A-C P < .001; functional: A-C P = .011; breast specific pain: A-B P < .001, A-C P < .001). Two qualitative themes were found: Treatment with the biggest impact on QoL, and Specific impact of RT on QoL. ConclusionsOmission of RT was associated with better QoL and functional and cosmetic outcomes. It was highly acceptable to patients. Clinicians should consider the potential for preserved QoL associated with treatment optimization via omission of RT in treatment planning for patients with EBC.

Peripheral blood mononuclear cells exhibit increased mitochondrial respiration after adjuvant chemo- and radiotherapy for early breast cancer.

Adjuvant chemo- and radiotherapy cause cellular damage to tumorous and healthy dividing cells. Chemotherapy has been shown to cause mitochondrial respiratory dysfunction in non-tumorous tissues, but the effects on human peripheral blood mononuclear cells (PBMCs) remain unknown. We aimed to investigate mitochondrial respiration of PBMCs before and after adjuvant chemo- and radiotherapy in postmenopausal patients with early breast cancer (EBC) and relate these to metabolic parameters of the patients. Twenty-three postmenopausal women diagnosed with EBC were examined before and shortly after chemotherapy with (n = 18) or without (n = 5) radiotherapy. Respiration (O2 flux per million PBMCs) was assessed by high-resolution respirometry of intact and permeabilized PBMCs. Clinical metabolic characteristics and mitochondrial DNA (mtDNA) content of PBMCs (mtDN relative to nuclear DNA) were furthermore assessed. Respiration of intact and permeabilized PBMCs from EBC patients significantly increased with adjuvant chemo- and radiotherapy (p = 6 × 10-5 and p = 1 × 10-7 , respectively). The oxygen flux attributed to specific mitochondrial complexes and respiratory states increased by 17-43% compared to before therapy initiation. Similarly, PBMC mtDNA content increased by 40% (p = 0.002). Leukocytes (p = 0.0001), hemoglobin (p = 0.0003), and HDL cholesterol (p = 0.003) concentrations decreased whereas triglyceride (p = 0.01) and LDL (p = 0.02) concentrations increased after treatment suggesting a worsened metabolic state. None of the metabolic parameters or the mtDNA content of PBMCs correlated significantly with PBMC respiration. This study shows that mitochondrial respiration and mtDNA content in circulating PBMCs increase after adjuvant chemo- and radiotherapy in postmenopausal patients with EBC. Besides the increased mtDNA content, a shift in PBMC subpopulation proportions towards cells relying on oxidative phosphorylation, who may be less sensitive to chemotherapy, might influence the increased mitochondrial respiration observed iafter chemotherapy.

Objective, Clinician- and Patient-Reported Evaluation of Late Toxicity Following Adjuvant Radiation for Early Breast Cancer: Long-Term Follow-Up Results of a Randomised Series.

Background and Purpose: This study aimed to differentially assess the frequency and severity of late radiation-induced toxicity following adjuvant whole-breast irradiation for early breast cancer with conventional fractionation (CF) and moderate hypofractionation (mHF). Materials and Methods: Patients recruited in a previous randomised controlled trial comparing acute toxicity between CF and mHF without disease recurrence were included in a post hoc analysis. Spectrophotometric and ultrasonographic examinations were performed for an objective evaluation and subsequent comparison of long-term skin toxicity. Furthermore, patient- and clinician-reported outcomes were recorded. Results: Sixty-four patients with a median age of 58 (37-81) years were included. The median follow-up was 57 (37-73) months. A total of 55% underwent CF and 45% mHF. A total of 52% received a sequential boost to the tumour bed. A significant decrease in mean L* (p = 0.011) and an increase in a* (p = 0.040) and b* values (p < 0.001) were observed, indicating hyperpigmentation. In comparison with the non-irradiated breast, there was a significant increase in both cutis (+14%; p < 0.001) and subcutis (+17%; p = 0.011) thickness, significantly more pronounced in CF patients (p = 0.049). In CF patients only, a sequential boost significantly increased the local cutis thickness and oedema compared to non-boost regions in the same breast (p = 0.001 and p < 0.001, respectively). Conclusions: mHF objectively resulted in reduced long-term skin toxicity compared to CF. A sequential boost increased the local fibrosis rate in CF, but not in mHF. This might explain the subjectively reported better cosmetic outcomes in patients receiving mHF and reinforces the rationale for favouring mHF as the standard of care.

Incidental Axillary Dose of Tomotherapy in Hypofractionated Whole Breast Radiotherapy for Early Breast Cancer: A Dosimetrical Analysis.

Background and Objectives: Intensity-modulated radiation therapy (IMRT) is becoming a more common method of performing whole breast irradiation (WBI) for early breast cancer. This study aimed to examine the incidental dose to the axillary region using tomotherapy, a unique form of IMRT. Patients and Methods: This study included 30 patients with early-stage breast cancer who underwent adjuvant WBI using TomoDirect IMRT. A hypofractionation scheme of 42.4 Gy delivered in 16 fractions was prescribed. The plan comprised of two parallel-opposed beams, along with two additional beams positioned anteriorly at gantry angles of 20° and 40° from the medial beam. The incidental dose received at axillary levels I, II, and III was evaluated using several dose-volume parameters. Results: The study participants had a median age of 51 years, and 60% had left-sided breast cancer. The mean dose of the axilla for levels I, II, and III were 15.5 ± 4.8 Gy, 14.9 ± 4.2 Gy, and 1.5 ± 1.6 Gy, respectively. Adequate coverage of the axilla, defined as V95%[%], was achieved for 4.7 ± 3.9%, 4.8 ± 3.7%, and 0 ± 0% for levels I, II, and III, respectively. The results were compared with those of previously published studies, and the axillary mean dose and V95%[%] of TomoDirect IMRT were low, comparable to other IMRT techniques, and lower than those of traditional tangential therapy. Conclusions: While incidental axillary radiation during WBI has been proposed to assist in regional disease control, the TomoDirect plan was demonstrated to decrease this dose, and a hypofractionation scheme would further lower its biological effectiveness. Future clinical studies should incorporate dosimetrical analysis of incidental axillary dose, in order to facilitate hypofractionated IMRT planning with risk-adjusted axilla coverage in early breast cancer.

Dose-escalated simultaneous integrated boost radiotherapy in early breast cancer (IMPORT HIGH): a multicentre, phase 3, non-inferiority, open-label, randomised controlled trial

A tumour-bed boost delivered after whole-breast radiotherapy increases local cancer-control rates but requires more patient visits and can increase breast hardness. IMPORT HIGH tested simultaneous integrated boost against sequential boost with the aim of reducing treatment duration while maintaining excellent local control and similar or reduced toxicity. IMPORT HIGH is a phase 3, non-inferiority, open-label, randomised controlled trial that recruited women after breast-conserving surgery for pT1-3pN0-3aM0 invasive carcinoma from radiotherapy and referral centres in the UK. Patients were randomly allocated to receive one of three treatments in a 1:1:1 ratio, with computer-generated random permuted blocks used to stratify patients by centre. The control group received 40 Gy in 15 fractions to the whole breast and 16 Gy in 8 fractions sequential photon tumour-bed boost. Test group 1 received 36 Gy in 15 fractions to the whole breast, 40 Gy in 15 fractions to the partial breast, and 48 Gy in 15 fractions concomitant photon boost to the tumour-bed volume. Test group 2 received 36 Gy in 15 fractions to the whole breast, 40 Gy in 15 fractions to the partial breast, and 53 Gy in 15 fractions concomitant photon boost to the tumour-bed volume. The boost clinical target volume was the clip-defined tumour bed. Patients and clinicians were not masked to treatment allocation. The primary endpoint was ipsilateral breast tumour relapse (IBTR) analysed by intention to treat; assuming 5% 5-year incidence with the control group, non-inferiority was predefined as 3% or less absolute excess in the test groups (upper limit of two-sided 95% CI). Adverse events were assessed by clinicians, patients, and photographs. This trial is registered with the ISRCTN registry, ISRCTN47437448, and is closed to new participants. Between March 4, 2009, and Sept 16, 2015, 2617 patients were recruited. 871 individuals were assigned to the control group, 874 to test group 1, and 872 to test group 2. Median boost clinical target volume was 13 cm3 (IQR 7 to 22). At a median follow-up of 74 months there were 76 IBTR events (20 for the control group, 21 for test group 1, and 35 for test group 2). 5-year IBTR incidence was 1·9% (95% CI 1·2 to 3·1) for the control group, 2·0% (1·2 to 3·2) for test group 1, and 3·2% (2·2 to 4·7) for test group 2. The estimated absolute differences versus the control group were 0·1% (-0·8 to 1·7) for test group 1 and 1·4% (0·03 to 3·8) for test group 2. The upper confidence limit for test group 1 versus the control group indicated non-inferiority for 48 Gy. Cumulative 5-year incidence of clinician-reported moderate or marked breast induration was 11·5% for the control group, 10·6% for test group 1 (p=0·40 vs control group), and 15·5% for test group 2 (p=0·015 vs control group). In all groups 5-year IBTR incidence was lower than the 5% originally expected regardless of boost sequencing. Dose-escalation is not advantageous. 5-year moderate or marked adverse event rates were low using small boost volumes. Simultaneous integrated boost in IMPORT HIGH was safe and reduced patient visits. Cancer Research UK.

PO-1266 Very stringent selection criteria are needed for intraoperative radiotherapy in early breast cancer

PO-1266 Very stringent selection criteria are needed for intraoperative radiotherapy in early breast cancer

Combining histological grade, TILs, and the PD-1/PD-L1 pathway to identify immunogenic tumors and de-escalate radiotherapy in early breast cancer: a secondary analysis of a randomized clinical trial

BackgroundThe implementation of immunological biomarkers for radiotherapy (RT) individualization in breast cancer requires consideration of tumor-intrinsic factors. This study aimed to investigate whether the integration of histological grade, tumor-infiltrating lymphocytes...

PO-1297 Safety & feasibility of SIB in extreme 1-week hypofractionated radiotherapy for early breast cancer

PO-1297 Safety & feasibility of SIB in extreme 1-week hypofractionated radiotherapy for early breast cancer

AA 1 Modern radiotherapy for early breast cancer

AA 1 Modern radiotherapy for early breast cancer

Intra-operative partial breast irradiation versus external whole breast irradiation for early breast cancer

Intra-operative radiotherapy (IORT) is a new alternative way to give radiation therapy. During surgery to remove breast cancer, radiation is given as a single dose directly to the area where the tumor used to be. The aim of the study was to compare the results of IORT as partial breast irradiation and external whole breast irradiation (EBRT) for early breast cancer in elderly patients after breast-conserving surgery. The results were retrospectively analyzed from a single institution. We report 7-year results for local control. Cross-sectional study. Between November 2012 and December 2019, 21 Gy partial breast irradiation was applied intra-operatively to 40 selected patients. Two of these patients were excluded from the study, and 38 patients were evaluated. Also, 38 patients who had EBRT and had similar properties to that of IORT patients were selected to compare the treatment results in terms of local control. SPSS version 21 was used for statistical analysis. Patient groups undergoing IORT and EBRT were analyzed with the Kolmogorov-Smirnov test. The groups were examined in terms of demographic features using t-test, and P < 0.05 was considered as statistically significant. Local recurrence rates were calculated by Kaplan-Meier analysis. The median follow-up time was 58 months (range 20-95 months). The local control was 100% in both groups, and no local recurrences were observed. IORT seems to be a safe and effective alternative to EBRT for early breast cancer in elderly patients.

Cost-effectiveness of 5 fraction and partial breast radiotherapy for early breast cancer in the UK: model-based multi-trial analysis

PurposeWe estimated the cost-effectiveness of 4 radiotherapy modalities to treat early breast cancer in the UK. In a subgroup of patients eligible for all modalities, we compared whole-breast (WB) and partial breast (PB) radiotherapy delivered in either 15 (WB15F, PB15F) or 5 fractions (WB5F, PB5F). In a subgroup ineligible for PB radiotherapy, we compared WB15F to WB5F.MethodsWe developed a Markov cohort model to simulate lifetime healthcare costs and quality-adjusted life years (QALYs) for each modality. This was informed by the clinical analysis of two non-inferiority trials (FAST Forward and IMPORT LOW) and supplemented with external literature. The primary analysis assumed that radiotherapy modality influences health only through its impact on locoregional recurrence and radiotherapy-related adverse events.ResultsIn the primary analysis, PB5F had the least cost and greatest expected QALYs. WB5F had the least cost and the greatest expected QALYs in those only eligible for WB radiotherapy. Applying a cost-effectiveness threshold of £15,000/QALY, there was a 62% chance that PB5F was the cost-effective alternative in the PB eligible group, and there was a 100% chance that WB5F was cost-effective in the subgroup ineligible for PB radiotherapy.ConclusionsHypofractionation to 5 fractions and partial breast radiotherapy modalities offer potentially important benefits to the UK health system.

Comparison of Short Term Clinical and Dosimetric Outcomes of Fast Forward vs. Hypofractionated Radiotherapy for Early Breast Cancer – A Single Center Experience

<h3>Purpose/Objective(s)</h3> To share the experience of planning, dosimetric evaluation and delivery of ultra-hypofractionated (fast forward-FF) versus hypofractionated (HF) radiotherapy in breast cancers treated at our center. <h3>Materials/Methods</h3> 60 patients (average age 44 years- range 32-65 years) of early [T1, T2N0] breast cancer (BC) treated between October 2020 and October 2021 were included. Plans of 15 patients of left BC by FF, left BC by HF, right BC by FF and right BC by HF were evaluated in terms of coverage and organs at risk (OAR) constraints. Patients were planned by field within field [FIF] planning for phase I (42.5 Gy/16# for HF and 26 Gy/5# for FF). Boost plans were generated by FIF/electron/conformal planning to a dose of 10-16 Gy @ 2 Gy/fraction. Deep inspiratory breath hold (DIBH) was used for left sided BC patients who were able to hold breath. PTV coverage goal was V95 more than or equal to 95%, V105 <7%, V107 < 2%. Constraints for FF were – lung V8<15%, heart V1.5<30%, V7<5%. Constraints for HF plans were – lung V20<20%, heart avg <3 Gy. 15 right sided BC patients were treated with FF and 15 by HF plans. For left sided BC, plans were generated for dosimetric comparison between FF and HF plans, but all patients were treated by HF plans. <h3>Results</h3> For left sided BC cases, high heart dose was seen in those with more heart volume, precordial location of boost volume and patients unable to do DIBH. All patients treated by FF had grade I skin reaction and 1/15 had wet desquamation in inframammary fold. Among patients treated by HF, majority patients had dry desquamation, 3/45 had wet desquamation in folds. Edema developed in FF by 2-3^rd fraction and by 7-9^th fraction in HF. Edema was milder in HF. The edema and skin changes resolved in 2-3 weeks. At 3 and 6 months, mild skin discoloration and minimal induration at post op site was seen which was similar in those treated by FF and HF. <h3>Conclusion</h3> Adequate coverage and OAR constraints can be met for FF as for HF plans. Radiation dermatitis is milder in FF arm and the edema is milder in the HF arm. Radiation of early breast cancer by FF is executable at independent centers with diligent planning with tight constraints and precise delivery.

Safety and Feasibility of Simultaneous Integrated Boost in Extreme 1-Week Hypofractionated Radiotherapy for Early Breast Cancer

<h3>Purpose/Objective(s)</h3> The phase 3 FAST-Forward trial reported that 26 Gy in 5 fractions (fx) over 1 week for early-breast cancer patients after breast conserving surgery was non-inferior to the standard 40 Gy in 15fx over 3 weeks for local tumor control and normal tissue effects. In this study, a sequential tumor bed boost was allowed (10 or 16 Gy in 2 Gy/fx) if required. The aim of our study is to evaluate the safety and feasibility of a simultaneous integrated boost (SIB) up to 29/30 Gy over 5fx in order to avoid treatment lengthening when a boost is indicated. <h3>Materials/Methods</h3> From March 2020 to December 2021, 126 patients eligible for 5fx-RT schedule were referred to our institution and selected for the analysis. A SIB to the tumor bed up to 29 Gy in 5fx of 5,8 Gy was indicated when any of the following criteria appeared: Age < 60 years, high-grade tumors and lymphovascular or perineural invasion. When positive margins were observed in the histological exam, a SIB up to 30 Gy in 5fx of 6 Gy was prescribed. Patient´s toxicity was assessed at 4 different points: During RT and at 1-, 6- and 12-months follow-up. Toxicity was evaluated using CTCAE 5.0 criteria. <h3>Results</h3> Mean follow-up was 6.25 months and mean age was 56 years (32-83). During RT course, no toxicities were observed. G1-2 dermatitis was observed in 9 patients at first month assessment, but all of them had disappeared at 6 months after RT. According to skin-color changes, 11% of the patients presented skin hyperpigmentation at first month assessment but in most cases was not observed in subsequent evaluations. Only 4% of the patients presented G1 fatigue and skin induration in the first medical visit after RT. No severe toxicities were found in any patient at any time during follow-up. Complete details are shown in table 1. In addition, one patient developed mastitis during the first month after RT but was easily solved with oral antibiotics. <h3>Conclusion</h3> According to our data, administration of SIB up to 29/30 Gy in 5fx is safe and feasible for early-breast cancer patients requiring adjuvant RT after breast conserving surgery. SIB could replace sequential boost in these patients shortening the RT treatment and improving patients' compliance and comfort. Further follow-up is needed in order to assess chronic toxicity.

Impact of preoperative magnetic resonance imaging on surgery and eligibility for intraoperative radiotherapy in early breast cancer.

We looked at the usefulness of magnetic resonance imaging (MRI) in decision-making and surgical management of patients selected for intraoperative radiotherapy (IORT). We also compared lesion size measurements in different modalities (ultrasound (US), mammogram (MMG), MRI) against pathological size as the gold standard. 63 patients eligible for IORT based on clinical and imaging criteria over a 34-month period were enrolled. All had MMG and US, while 42 had additional preoperative MRI for locoregional preoperative staging. Imaging findings and pathological size concordances were analysed across the three modalities. MRI changed the surgical management of 5 patients (11.9%) whereby breast-conserving surgery (BCS) and IORT was cancelled due to detection of satellite lesion, tumor size exceeding 30mm and detection of axillary nodal metastases. Ten of 42 patients (23.8%) who underwent preoperative MRI were subjected to additional external beam radiotherapy (EBRT); 7 due to lymphovascular invasion (LVI), 2 due to involved margins, and 1 due to axillary lymph node metastatic carcinoma detected in the surgical specimen. Five of 21 (23.8%) patients without prior MRI were subjected to additional EBRT post-surgery; 3 had LVI and 2 had involved margins. The rest underwent BCS and IORT as planned. MRI and MMG show better imaging-pathological size correlation. Significant increase in the mean 'waiting time' were seen in the MRI group (34.1 days) compared to the conventional imaging group (24.4 days). MRI is a useful adjunct to conventional imaging and impacts decision making in IORT. It is also the best imaging modality to determine the actual tumour size.

Abstract OT1-01-01: A randomized, pragmatic trial investigating the timing of radiotherapy and endocrine in patients with early stage breast cancer (REaCT-RETT trial)

Abstract The optimal timing of commencing adjuvant endocrine therapy (ET) relative to adjuvant radiotherapy (RT) (i.e. concurrent with or sequential to radiotherapy) remains unknown. A systematic review performed by our team was unable to answer this question due to a lack of high quality, randomized data on concurrent versus sequential ET and RT. Surveys of physicians confirmed this uncertainty and highlighted theoretical concerns for increased side effects with concurrent treatment. Respondents showed keen interest in obtaining real world, randomized data to guide clinical practice. REaCT-RETT is a pragmatic, randomized, non-inferiority trial comparing concurrent and sequential ET and RT in early breast cancer (EBC). The primary endpoint will assess the change in ET side effects at baseline and 3 months post radiation, using the Functional Assessment of Cancer Therapy-Endocrine Subscale (FACT-ES), with primary analysis based on an analysis of covariance (ANCOVA). With a sample size of 176 patients (88 per arm), an ANCOVA would have 80% power (α=0.05) to detect effect sizes as small as 0.25 regardless of the correlation with covariates. It is hypothesized that concurrent therapy will be non-inferior to sequential therapy in terms of ET side effects. Secondary endpoints will examine RT toxicity, ET compliance, quality of life, and cost-effectiveness. Patients with HR positive EBC planned to receive both adjuvant ET and RT were eligible. Patients who previously received ET for invasive breast cancer, or RT in the same breast, were excluded. The trial is conducted by The Ottawa Hospital’s (TOH) innovative Rethinking Clinical Trials (REaCT) program (https://react.ohri.ca/) which strives to improve access to patient-centered, pragmatic clinical trials by removing barriers for patients and researchers. Integral features of the program include broad eligibility criteria, a verbal consent model, and pragmatic data collection and assessment procedures. REaCT is the largest pragmatic cancer clinical trials program in Canada, with over 3,200 patients randomized in 18 clinical trials at 15 sites across Canada. REaCT-RETT accrued patients from September 2019 to January 2021. Data collection is ongoing, with final patient follow up expected April 2022. The timing of accrual provided a unique opportunity to adapt in response to restrictions due to the COVID-19 pandemic, which began to impact trial sites in March 2020. The target sample size was met with 262 patients randomized (1:1) across 3 sites in Ontario, 98% from TOH. A mean of 19 patients/month were accrued prior to the pandemic, compared to a mean of 13 patients/month after March 2020. Twenty-two patients were removed due to withdrawal of consent, ineligibility, or physician choice, and the pandemic was not a significant contributing factor. Since March 2020 there have been 772 patient follow ups, of which 47% (364/772) have been virtual. Only 10% (102/1028) of trial mandated appointments have been missed to date. Compliance with baseline and 3-month FACT-ES questionnaires for the primary endpoint in evaluable patients was 90% (215/240) and 83% (198/240), respectively. The pandemic posed several challenges to the REaCT-RETT study including a decline in patient accrual, poor accrual at peripheral sites due to delayed opening, and a rapid switch to virtual patient care. However, the nimble REaCT methodology enabled virtual patient consent and data collection during the pandemic, allowing the trial to continue successfully, with final data expected for presentation summer 2022. Finally, despite the challenges of COVID-19 we have seen that patients and physicians remain interested in research, and we are applying valuable lessons learned to forthcoming REaCT trials to strengthen their performance during and beyond the ongoing pandemic. Citation Format: Sharon F Mc Gee, Mark Clemons, Michelle Liu, Mashari Jemaan Alzahrani, Terry Ng, Arif Awan, Sandeep Sehdev, John Hilton, Jean Michel Caudrelier, Marie France Savard, Lesley Fallowfield, Vikaash Kumar, Orit Freedman, Dean Fergusson, Gregory Pond, Brian Hutton, Jean Marc Bourque. A randomized, pragmatic trial investigating the timing of radiotherapy and endocrine in patients with early stage breast cancer (REaCT-RETT trial) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-01-01.

Comparison between the use of hypofractionated and conventionally fractionated radiotherapy in early breast cancer: A single-center real-world study in Taiwan

This study aimed to analyze the long-term outcomes of hypofractionated whole-breast irradiation (WBI) (HF-WBI) compared with those of conventionally fractionated WBI (CF-WBI) for early breast cancer treated with breast-conservation surgery (BCS) and adjuvant WBI in Taiwan. This study included patients treated at our institution between 2012 and 2016. All patients with early breast cancer received BCS (pT1-2, pN0, M0) and adjuvant WBI through one of two treatment schemes. Propensity score matching analysis was conducted to create comparable cohorts. The major result is ipsilateral breast tumor recurrence (IBTR) rates and overall survival rates. A total of 869 patients with early-stage breast cancer received adjuvant HF-WBI or CF-WBI were included. After matching, 718 patients were separated into two groups of the same number. With a median follow-up of 66 months, seven cases of IBTR were noted (three for CF, four for HF). There were no significant differences between the HF-WBI and CF-WBI groups in 5-year IBTR rates (0.9% vs 0.6%, P=0.3887, 95% CI [0.25-7.79]) and 5-year overall survival rates (98.1% vs 98.9%, P=0.4702, 95% CI [0.32-3.49]). In our institution, the use of HF-WBI increased significantly from 5% before 2012 (Q3) to 92% in 2016 (Q4). There was no significant difference in grade 1-2 toxicity between the two treatment groups. Fewer cases of grade 3 skin toxicity noted in the HF-WBI group (zero vs four events). HF-WBI had similar IBTR, OS and toxicity to CF-WBI.

European Society for Radiotherapy and Oncology Advisory Committee in Radiation Oncology Practice consensus recommendations on patient selection and dose and fractionation for external beam radiotherapy in early breast cancer.

High-quality randomised clinical trials testing moderately fractionated breast radiotherapy have clearly shown that local control and survival is at least as effective as with 2 Gy daily fractions with similar or reduced normal tissue toxicity. Fewer treatment visits are welcomed by patients and their families, and reduced fractions produce substantial savings for health-care systems. Implementation of hypofractionation, however, has moved at a slow pace. The oncology community have now reached an inflection point created by new evidence from the FAST-Forward five-fraction randomised trial and catalysed by the need for the global radiation oncology community to unite during the COVID-19 pandemic and rapidly rethink hypofractionation implementation. The aim of this paper is to support equity of access for all patients to receive evidence-based breast external beam radiotherapy and to facilitate the translation of new evidence into routine daily practice. The results from this European Society for Radiotherapy and Oncology Advisory Committee in Radiation Oncology Practice consensus state that moderately hypofractionated radiotherapy can be offered to any patient for whole breast, chest wall (with or without reconstruction), and nodal volumes. Ultrafractionation (five fractions) can also be offered for non-nodal breast or chest wall (without reconstruction) radiotherapy either as standard of care or within a randomised trial or prospective cohort. The consensus is timely; not only is it a pragmatic framework for radiation oncologists, but it provides a measured proposal for the path forward to influence policy makers and empower patients to ensure equity of access to evidence-based radiotherapy.

Comparison of the Oncological Efficacy Between Intraoperative Radiotherapy With Whole-Breast Irradiation for Early Breast Cancer: A Meta-Analysis

BackgroundIntraoperative radiotherapy (IORT) and whole-breast irradiation (WBI) are both effective radiotherapeutic interventions for early breast cancer patients undergoing breast-conserving surgery; however, an issue on whether which one can entail the better prognosis is still controversial. Our study aimed to investigate the 5-year oncological efficacy of the IORT cohort and the WBI cohort, respectively, and compare the oncological efficacy between the cohorts.Materials and MethodsWe conducted a computerized retrieval to identify English published articles between 2000 and 2021 in the PubMed, the Web of Science, the Cochrane Library, and APA PsycInfo databases. Screening, data extraction, and quality assessment were performed in duplicate.ResultsA total of 38 studies were eligible, with 30,225 analyzed participants. A non-comparative binary meta-analysis was performed to calculate the weighted average 5-year local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) in the two cohorts, respectively. The LRFS, DMFS, and OS (without restriction on the 5-year outcomes) between the two cohorts were further investigated by a comparative binary meta-analysis. The weighted average 5-year LRFS, DMFS, and OS in the IORT cohort were 96.3, 96.6, and 94.1%, respectively, and in the WBI cohort were 98.0, 94.9, and 94.9%, respectively. Our pooled results indicated that the LRFS in the IORT cohort was significantly lower than that in the WBI cohort (pooled odds ratio [OR] = 2.36; 95% confidential interval [CI], 1.66–3.36). Nevertheless, the comparisons of DMFS (pooled OR = 1.00; 95% CI, 0.76–1.31), and OS (pooled OR = 0.95; 95% CI, 0.79–1.14) between the IORT cohort with the WBI cohort were both not statistically significant.ConclusionsDespite the drastically high 5-year oncological efficacy in both cohorts, the LRFS in the IORT cohort is significantly poorer than that in the WBI cohort, and DMFS and OS do not differ between cohorts.